Magnesium oxide-crosslinked low-swelling citrate-based mussel-inspired tissue adhesives

Xili Lu; Sanjun Shi; Hanmei Li; Ethan Gerhard; Zhihui Lu; Xinyu Tan; Wenliang Li; Kevin M Rahn; Denghui Xie; Guodong Xu; Fang Zou; Xiaochun Bai; Jinshan Guo; Jian Yang

doi:10.1016/j.biomaterials.2019.119719

Magnesium oxide-crosslinked low-swelling citrate-based mussel-inspired tissue adhesives

Biomaterials. 2020 Feb:232:119719. doi: 10.1016/j.biomaterials.2019.119719. Epub 2019 Dec 23.

Authors

Xili Lu¹, Sanjun Shi², Hanmei Li³, Ethan Gerhard⁴, Zhihui Lu⁵, Xinyu Tan⁶, Wenliang Li⁷, Kevin M Rahn⁴, Denghui Xie⁶, Guodong Xu⁸, Fang Zou⁸, Xiaochun Bai⁹, Jinshan Guo¹⁰, Jian Yang¹¹

Affiliations

¹ Institute of Materials Processing and Intelligent Manufacturing, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, China; Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
² Center of Nanomedicine and Department of Department of Anesthesiology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, 02115, USA.
³ Key Laboratory of Coarse Cereal Processing (Ministry of Agriculture and Rural Affairs), College of Pharmacy and Biological Engineering, Chengdu University, Chengdu, 610106, China.
⁴ Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
⁵ Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China; Academy of Orthopedics, Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510280, China.
⁶ Academy of Orthopedics, Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510280, China.
⁷ Center for Nanomaterials, School of Pharmacy, Jilin Medical University, Jilin, Jilin, 132013, China.
⁸ Institute of Materials Processing and Intelligent Manufacturing, College of Materials Science and Chemical Engineering, Harbin Engineering University, Harbin, 150001, China.
⁹ Academy of Orthopedics, Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510280, China; Department of Cell Biology, Key Laboratory of Mental Health of the Ministry of Education, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China.
¹⁰ Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA; Department of Histology and Embryology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China; Academy of Orthopedics, Provincial Key Laboratory of Bone and Joint Degenerative Diseases, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong Province, 510280, China. Electronic address: jsguo4127@smu.edu.cn.
¹¹ Department of Biomedical Engineering, Materials Research Institute, The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 16802, USA. Electronic address: jxy30@psu.edu.

PMID: 31901688
DOI: 10.1016/j.biomaterials.2019.119719

Abstract

Tissue adhesives are commonly used in surgeries and regenerative engineering for the repair and regeneration of topical and internal wounds on tissues and organs such as skin, heart, blood vessels, and bone. However, achieving rapid crosslinking, strong wet adhesion and cohesion strengths, and minimal cytotoxicity remains a critical roadblock for clinical translation. Herein, in contrast to harsh and cytotoxic oxidants, magnesium oxide (MgO) particles were found to facilitate rapid crosslinking for injectable citrate-based mussel-inspired tissue bioadhesives synthesized by reacting citric acid, PEG-PPG-PEG diol and dopamine (iC-EPE). Our results confirmed the role of MgO particles as both crosslinkers and composite fillers to concurrently enhance bioadhesive cohesion and adhesion. iC-EPE crosslinked by MgO with/without sodium periodate (PI) exhibit enhanced mechanical strengths (1.0 Mpa < tensile strength ≤ 4.5 MPa) compared to that of iC-EPE crosslinked only by PI (~0.75 MPa), high adhesion strength (up to 125 kPa, 8 fold that of fibrin glue (~15 kPa)), tunable degradability (full degradation from <1 week to > 1 month), excellent in vitro and in vivo biocompatibility, encouraging anti-bacterial performance, and favorable wound closure efficacy. Thus, MgO crosslinked bioadhesives possess great potential for a wide range of applications in surgery and regenerative engineering.

Keywords: Citrate; Magnesium oxide (MgO); Mussel-inspired adhesion; Tissue adhesives; Wound closure.

MeSH terms

Adhesives
Animals
Bivalvia*
Citrates
Citric Acid
Magnesium Oxide
Tissue Adhesives*

Substances

Adhesives
Citrates
Tissue Adhesives
Citric Acid
Magnesium Oxide